Heterogeneous expression of melanoma antigen (hMAGE) mRNA in mesenchymal neoplasia

Recommendations have been advanced recently for the use of cancer/testis (CT) immunotherapy against sarcomas. CT antigens are encoded by cancer-germline genes (e.g., hMAGE family) that are expressed in tumors and male germline cells but typically not in normal tissues. At present, little information is available regarding CT expression in mesenchymal neoplasms, and it remains uncertain whether CT immunotherapy will serve as a viable alternative or adjunct to current sarcoma therapies involving resection, followed by adjuvant radiotherapy and/or chemotherapy. In this study, hMAGEA2, hMAGEA3, hMAGEA4, and hMAGEC1 mRNA content in 21 benign mesenchymal tumors (representing seven histotypes) and 28 primary sarcomas (10 histotypes) was inventoried using real-time-PCR and then compared against hMAGE mRNA expression in non-sarcomatous malignancies, three cell lines, and muscle. hMAGEA2, hMAGEA3, and hMAGEC1 transcripts were infrequent in mesenchymal tissues in general, whereas hMAGEA4 mRNA was present in 84% of all mesenchymal tumors, 100% of non-sarcomatous tumors, all three cell lines, and in four of five muscle samples. Although hMAGEA4 mRNA was detected in four of five muscle preparations, there was no indication that the mRNA was translated into protein. The presence of hMAGEA4 mRNA in muscle, plus the inconsistent and infrequent occurrence of hMAGEA2, hMAGEA3, and hMAGEC1 mRNA within and among mesenchymal tumor histotypes, makes these four hMAGE antigens unlikely candidates for sarcoma-specific immunotherapy.